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PubMed1993

Characterization and clinical relevance of liver-pancreas antibodies in autoimmune hepatitis.

The isolation of a marker antigen from rat liver and pancreas tissue, which reacts with antibodies in a subtype of autoimmune hepatitis by complement fixation test, enzyme-linked immunosorbent assay and Western blot, is described. The liver-pancreas antigen could be detected in tissue from different human or animal organs, but liver and pancreas yielded the highest activity. A highly specific antigen fraction was obtained by gel filtration and ion exchange chromatography with a 100,000 g supernatant from rat liver tissue, and this preparation was shown to be devoid of nuclear, mitochondrial and microsomal antigens and cytokeratin 8 and 18, as demonstrated by appropriate marker antibodies. These data and absorption studies with cell organelles indicate that liver-pancreas antigen is a cytosolic protein. By Western blotting, two major epitopes at molecular weights 52 kD and 48 kD could be visualized. Sera from 175 patients previously shown to have high complement-fixing activity to a nonpurified liver-pancreas antigen fraction were further analyzed. All were positive by enzyme-linked immunosorbent assay with the purified liver-pancreas antigen fractions, and 111 were also positive by Western blot. Eighty-six sera reacted with the 52-kD determinant, 33 with the 48-kD determinant and 2 with both determinants. In 117 of the 175 patients, antibody to liver-pancreas antigen was associated with other autoantibodies known to characterize subgroups of autoimmune hepatitis. Thus 19 patients had antibodies to nuclei and 96 to actin but none to liver-kidney microsomes, hereby suggesting that antibody to liver-pancreas antigen may define another subgroup of autoimmune hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Consequences of pancreas transplantation.

PKT has become an important option in selected IDDM patients being considered for kidney transplantation because of its ability to offer superior glycemic control and improved quality of life. As both kidney graft survival and overall mortality are comparable following PKT and kidney transplantation alone at many centers, neither the survival of the patient nor the success of the kidney transplant need be jeopardized by the addition of a pancreas graft. The greater morbidity of PKT can be justified by the evidence that a pancreas graft will prevent recurrent diabetic nephropathy, result in greater improvements in sensory/motor neuropathy, and in some but not all studies, cause greater stabilization of eye disease. Improvements in lipid profiles observed after PKT but not after kidney transplant alone may predict better cardiovascular outcomes as well. Determination of who should receive an isolated pancreas transplant is more complex. Success rates are lower than after PKT. It remains important to ascertain that the candidate is susceptible to diabetic complications, or has repeated bouts of hypoglycemia or ketoacidosis unresponsive to other measures to justify the risks of long-term immuno-suppression. More difficult to determine is whether or when individuals who have advancing diabetic complications yet relatively preserved renal function (creatinine clearance > 70 mL/min) should become candidates. For now, each individual is considered on a case by case basis and the relative risks and benefits for each individual are carefully assessed. However, patient selection will be greatly aided by further research assessing the long-term risks and benefits of all types of pancreas transplantation. Pancreas transplantation will remain an important option in the treatment of IDDM until alternative strategies are developed that can provide equal glycemic control with less or no immunosuppression or less overall morbidity. Most of the research to date has concentrated on the consequences of pancreas transplantation on microvascular complications. However, cardiovascular disease events represent the greatest cause of mortality in pancreas transplant candidates. Thus, changes in cardiovascular risk after pancreas transplantation may be more important to long-term survival than any other factor and should receive greater attention in future studies.

Adolescent↗
PubMed1996

[Combined renal-pancreas transplantation in the treatment for chronic renal insufficiency of diabetic origin . Results from the Pitie Urology Clinic].

Between 1989 and 1995, 32 patients underwent combined kidney-pancreas transplantation for diabetic chronic renal failure. Only one of these patients received an isolated pancreas following cessation of function of a previously implanted segmental pancreas. The surgical technique always consisted of pure retroperitoneal transplantation into the right iliac fossa of a total pancreas transplant with duodenovesical anastomosis. The postoperative complications included one death on D10 from pulmonary vein thrombosis in a patient with sickle cell anaemia and early loss of the transplanted pancreas due to venous thrombosis. Nine patients underwent at least one surgical revision, due to a leaking duodenovesical anastomosis in 8 cases. With a mean follow-up of 33 +/- 20 months, the results demonstrate, apart from the early death indicated above, another death at 50 months of a patient who had lost his pancreas due to early venous thrombosis and who died with a functioning kidney. 23 of the 30 surviving patients have a functioning kidney and pancreas (79%), i.e. 74% of the total population of 32 patients. Loss of pancreatic function was surgical in two cases (one case of infection of the transplant site, one case of thrombosis), vascular in one case due to rupture of a mycotic aneurysm into the duodenum and immunological in three cases: two of these pancreases retained partial function allowing perfect blood glucose control with less than 10 units of ordinary insulin per day. Lastly, a perfectly functioning pancreas was removed 13 months after transplantation because of renal rejection not controlled by reinforced immunosuppression. Compared to the data of the international registry, these results demonstrate the value of the retroperitoneal approach used in this series and the improvement of the results obtained with increasing experience of the transplant team.

Adult↗
PubMed1996

[Hypoechogenic aspects of the ventral embryonic cephalic pancreas: a large prospective clinical study].

Global echogenicity of the normal pancreas increases essentially with lipomatous involution which is common with aging. However, the two embryologic different parts of the cephalic pancreas may present a different echogenicity: the "embryologic ventral" pancreas-posterior cephalic pancreas + uncinate process-is then hypoechoic because of less fatty involution. It is important to distinguish such normal variant from a pathological process. The clinical prevalence and morphologic characteristics of this normal variant have been prospectively studied in a large series of 446 patients including 275 females and 171 males. The study confirms the proportional increase of pancreatic echogenicity with age. The variant has a sharp female predominance: 27.5% of males vs 43.3% females, corresponding to a sex ratio of 1:1.52. Hypoechoic ventral embryologic cephalic pancreas is never encountered before the age of 25 and is most frequent in middle aged females with moderately echoic pancreas. There is not any difference in global cephalic pancreatic thickness between our positive group and a negative group of reference of 66 patients. These observations rather plead a genetic uneven fatty involution in positive cases instead of ventral pancreas atrophy in negative cases. The morphological and biometric characteristics of the hypoechoic embryologic ventral pancreas are rather stable. These are relatively independent from age, sex, and global pancreatic echogenicity.

Adult↗
PubMed1996

Adenine nucleotide metabolism of canine pancreas graft preserved by the two-layer (euro-collins' solution/perfluorochemical) method after reperfusion.

We have demonstrated that oxygenation of a pancreas during preservation by the two-layer method leads continued ATP production to maintain cellular integrity and produces an extended period of preserved pancreatic viability. In this study, we examined whether the pancreas grafts preserved by the two-layer method maintained adenine nucleotides pool as substrates for ATP synthesis before reperfusion and had the ability to synthesize ATP promptly and to recover energy charge potential (ECP) of the pancreas graft on reperfusion. After preservation by the two-layer cold storage method using EC for 48 hrs (group 1, n = 5), or simple cold storage in EC for 48 hrs (group 2, n = 5), canine pancreas grafts were autotransplanted. In control (group 3, n = 5), canine pancreas grafts were autotransplanted without preservation. Tissue adenine nucleotides concentrations were measured using high performance liquid chromatography (HPLC) before and after preservation, before reperfusion and after 1 hr- and 2 hr-reperfusion. Graft survival rates were 5/5, 0/5, and 5/5, in groups 1, 2 and 3, respectively. Total adenine nucleotides before reperfusion in group 1 was almost same levels as group 2 (7.41 +/- 1.47 vs 6.64 +/- 2.23 mumol/g dry weight, N.S.). Furthermore, ATP tissue levels in group 1 before reperfusion was 2.90 +/- 0.51 mumol/g dry weight and almost same levels as group 2 (2.03 +/- 0.68 mumol/g dry weight, N.S.). However, tissue ATP levels in group 1 after 2 hrs of reperfusion (6.71 +/- 1.19 mumol/g dry weight) were significantly higher than group 2 (4.51 +/- 0.51 mumol/g dry weight, P < 0.05), and almost same levels as control (group 3) (6.32 +/- 1.62 mumol/g dry weight, N.S.). In addition, ECP in group 1 and 3 (0.90 +/- 0.03 and 0.83 +/- 0.09, respectively) after 2 hr-reperfusion, were significantly higher than the value in group 2 (0.73 +/- 0.09, P < 0.01 and P < 0.05, respectively). It was clear that recovery of ATP on reperfusion was not depend on the residual nucleotides pool before reperfusion but the ability of the pancreas graft to recover tissue ATP levels and energy charge potential after reperfusion. We conclude that oxygenation of the pancreas graft during preservation by the two-layer method allows for ATP synthesis which is essential in maintaining cellular integrity and leads to maintain the graft's ability to recover ATP levels and energy charge potential promptly after reperfusion. Consequently the pancreas graft survives.

Adenine Nucleotides↗
PubMed1998

Epigastric pain and sonographic assessment of the pancreas in dengue hemorrhagic fever.

PURPOSE: This study reports the sonographic features of the pancreas in children who have dengue hemorrhagic fever (DHF) with epigastric pain, evaluates pancreatic abnormalities as the source of this pain, and relates sonographic findings, DHF status, and serum levels of amylase and lipase. METHODS: Over 3.5 years, real-time sonographic examination of the pancreas was prospectively performed in 148 children (age range, 5 months-14 years) who had DHF with epigastric pain. The DHF diagnosis was confirmed by serologic examination and viral isolation. RESULTS: Of the 142 children included in this study, 72 had mild DHF (grade I or II) and 70 had severe DHF (grade III or IV). An enlarged pancreas was found in 41 patients (29%), 10 (14%) of whom had mild DHF and 31 (44%) of whom had severe DHF. The pancreas was hyperechoic relative to the liver in 36 patients (25%), isoechoic in 98 (69%), and hypoechoic in 8 (6%). CONCLUSIONS: The majority of patients with DHF and epigastric pain do not have an enlarged pancreas, different echogenicity of the pancreas compared with the liver, or a dilated pancreatic duct. Thus, pathologic changes of the pancreas cannot be the only cause of epigastric pain in DHF patients. Increased serum levels of amylase and lipase are commonly seen in patients with severe DHF and an enlarged pancreas.

Abdominal Pain↗
PubMed1988

Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists.

Epidemiologic studies of diet and pancreas cancer are few, and include ecologic comparisons and a limited number of prospective and case-control studies. Foods and/or nutrients that have been suggested to be associated with increased risk of this cancer include total fat intake, eggs, animal protein, sugar, meat, coffee and butter. Consumption of raw fruits and vegetables has been consistently associated with decreased risk. Dietary habits and medical history variables were evaluated in a prospective study of fatal pancreas cancer among 34,000 California Seventh-day Adventists between 1976 and 1983. Forty deaths from pancreas cancer occurred during the follow-up period. Compared to all US whites, Adventists experienced decreased risk from pancreas cancer death (standardized mortality ratio [SMR] = 72 for men; 90 for women), which was not statistically significant. Although there was a suggestive relationship between increasing meat, egg, and coffee consumption and increased pancreatic cancer risk, these variables were not significantly related to risk after controlling for cigarette smoking. However, increasing consumption of vegetarian protein products, beans, lentils, and peas as well as dried fruit was associated with highly significant protective relationships to pancreas cancer risk. A prior history of diabetes was associated with increased risk of subsequent fatal pancreas cancer, as was a history of surgery for peptic or duodenal ulcer. A history of tonsillectomy was associated with a slight, nonsignificant protective relationship as was history of various allergic reactions. These findings suggest that the protective relationships associated with frequent consumption of vegetables and fruits high in protease-inhibitor content are more important than any increase in pancreas cancer risk attendant on frequent consumption of meat or other animal products. Furthermore, the previously reported positive associations between diabetes and abdominal surgery and pancreas cancer risk are supported in these data.

Adult↗
PubMed1995

Coffee consumption not associated with risk of pancreas cancer in Finland.

BACKGROUND: Coffee consumption has been brought to focus as a possible risk factor for pancreas cancer. After having reviewed the available evidence, an International Agency for Research on Cancer working group concluded in 1991 that the evidence in humans that coffee drinking is carcinogenic in the pancreas is "inadequate," since the available data were considered suggestive of a weak relationship with high levels of coffee consumption, but the possibility that this was due to bias or confounding was judged tenable. METHODS: The association between coffee consumption and pancreas cancer risk was examined in a case-referent study in Finland. Data on coffee consumption 20 years prior to the diagnosis of cancer were obtained from the next of kin of 662 cases of pancreas cancer and 1,770 referent (stomach, colon, and rectum) cancers. The results were expressed as crude and age-, gender-, and tobacco smoking-adjusted odds ratios and 95% confidence intervals for three daily coffee dose categories 20 years prior to cancer diagnosis. RESULTS: The data failed to demonstrate any association between coffee consumption and risk for pancreas cancer. The crude odds ratios varied between 0.7 (95% confidence interval 0.3-1.5) and 1.3 (0.7-2.6), the adjusted ones between 0.5 (0.2-1.2) and 1.1 (0.6-2.1) in the different daily dose categories of coffee and between contrasts with the three referent cancers. The highest odds ratios were associated with the contrast between pancreas and colon cancer, the lowest between pancreas and rectum cancer. Adjustment for gender, age, and tobacco smoking slightly decreased the values of the odds ratios. The power of the study was low, however, to detect possible weak increases associated with coffee consumption. CONCLUSIONS: The results are unlikely to be negatively biased, and are compatible with the majority of epidemiologic results advanced, suggesting no positive association between coffee consumption and the risk of pancreas cancer.

Case-Control Studies↗
PubMedDate not supplied

Duodenum-preserving resection of the head of the pancreas in chronic pancreatitis with inflammatory mass in the head.

In 141 patients with chronic pancreatitis and an inflammatory enlargement of the head of the pancreas, a duodenum-preserving resection of the head of the pancreas was performed within a 16-year period. The hospital mortality was 0.7%; the late mortality was 5%. Seventy-seven percent of the patients were completely free of abdominal pain; 67% returned to their former occupation. After a follow-up period of 3.6 years, glucose metabolism was unchanged in 81.7% of the patients, in 10.1% it deteriorated, and in 8.3% it improved permanently. In patients with severe chronic pancreatitis and an inflammatory mass in the head of the pancreas, a duodenum-preserving resection of the head of the pancreas is an alternative procedure to the Whipple operation. The surgical technique of the duodenum-preserving resection includes 2 major steps: first, subtotal resection of the head of the pancreas conserving the duodenum; second, restitution of the exocrine pancreatic secretory flow from the body and tail of the pancreas by using the first jejunal loop as an interposition. In comparison to the Whipple procedure, the duodenum-preserving resection of the head of the pancreas in chronic pancreatitis spares the patient a gastric resection, a duodenectomy, and a common bile duct resection. With respect to long-lasting pain relief and preservation of the endocrine function of the pancreas, duodenum-preserving resection of the head is a highly effective surgical procedure with a low early and late morbidity and mortality due to the limited surgical resection.

Chronic Disease↗
PubMed1998

Treatment of pancreas head carcinoma in a 91-yr-old man. Report of a case successfully treated with pylorus-preserving pancreatoduodenectomy.

The case of a 91-yr-old man who had a tumor of the pancreas head successfully resected is reported. He was admitted to our hospital because of obstructive jaundice, and then percutaneous transhepatic biliary drainage (PTBD) was performed. Cholangiography via PTBD tube showed marked stenosis of the bile duct in the head of the pancreas. Endoscopic retrograde pancreatography (ERP) showed obstruction of the main pancreatic duct in the head of the pancreas, and carcinoma in the head of the pancreas was diagnosed. Abdominal angiography showed stenosis of the celiac trunk caused by compression from the median arcuate ligament, but no tumor stain or encasement in the pancreas was detected. Because the patient had lived an extremely healthy life and had no serious concurrent disease before admission, laparotomy was performed. The tumor in the head of the pancreas was about 2 cm in diameter and restricted inside the pancreas. Pylorus-preserving pancreatoduodenectomy (PpPD) with regional lymph node dissection was performed. The tumor was 1.5 cm in its maximal diameter, and histopathologically was diagnosed as an invasive ductal carcinoma of the pancreas with moderately differentiated tubular adenocarcinoma. The patient had an uneventful postoperative course and now, 3 yr after surgery, he is doing very well and leading a normal daily life.

Aged↗
PubMed2000

A novel technique for multiple pancreatectomies: removal of unicinate process of the pancreas combined with medial pancreatectomy.

Preservation of normal pancreatic tissue in the surgical treatment of benign tumors of the pancreas offers advantages over more extended pancreatic resections. Removal of the uncinate process of the pancreas with the preservation of Wirsung's duct allows resection of a localized tumor within the uncinate process of the pancreas, maintains the flow of pancreatic juice into the duodenum, and preserves the dorsal part of the head of the gland. A pancreatic duct stent is particularly useful to identify the pancreatic duct (Wirsung's duct) intraoperatively to avoid injury which causes postoperative pancreatic leak. We have developed and employed a novel technique whereby tumors are completely excised, in combination with medial pancreatectomy, for the management of multiple mucin-producing tumors of the pancreas localized in the uncinate process and in the body of the pancreas. The cut end of the head of the pancreas is closed by interrupted sutures. Reconstruction for the distal pancreas is effected with a Roux-en-Y pancreatico-jejunostomy to the tail of the pancreas. Recovery was uncomplicated in our patient, with no endocrine or exocrine pancreatic insufficiency after 2-year follow-up.

Adenocarcinoma, Mucinous↗
PubMed2000

Ultrasonically activated scalpel is an effective tool for cutting the pancreas in biliary-pancreatic surgery: experimental and clinical studies.

The ultrasonically activated scalpel, a new tool for cutting and coagulating tissue, uses high-frequency ultrasonic vibrations, and has been widely employed in the field of laparoscopic surgery. We evaluated its usefulness for cutting the pancreas in biliary-pancreatic surgery. We planned experimental and clinical studies using an ultrasonically activated scalpel (harmonic scalpel) for cutting the pancreas. The harmonic scalpel was set up at a power level of 3 (75% of full power) in the knife mode. In the experimental study, using dogs, cutting of the pancreas with the harmonic scalpel resulted in significantly less bleeding and significantly less histological tissue damage to the cut stumps than cutting of the pancreas with an electric or a regular scalpel. In the clinical study: (1) the hemostatic effect of the harmonic scalpel was excellent or good in any condition of the pancreas; (2) of 50 stumps of the main pancreatic duct cut with the harmonic scalpel, the stump was easily found in 48 (96%), while ultrasonography was necessary to find the remaining 2 stumps in soft pancreas; (3) in 41 anastomoses (29 soft and 12 hard pancreas) there were no postoperative pancreatic fistulae. These results indicate that the ultrasonically activated scalpel is an effective tool for cutting the pancreas in biliary-pancreatic surgery.

Animals↗
PubMed1978

Prospective evaluation of gray scale ultrasonography in the diagnosis of pancreas cancer.

One hundred thirty-four patients suspected of having pancreas cancer successfully underwent gray scale ultrasound examination of the pancreas. The prospective ultrasound findings were correlated with the final diagnoses, laparotomy findings, and pathology findings. Fifty-four patients had pancreas cancer, confirmed by resection or biopsy in all cases. On ultrasonography, the pancreas was correctly reported to have abnormalities in sixty-one of seventy-eight patients (78 per cent) and correctly reported to have no abnornalities in thirty-eight of fifty-six patients (68 per cent). A correct ultrasound diagnosis of pancreas cancer was made for forty-four of fifty-six patients (81 per cent), and there were thirteen false-positive reports. Ninety-four percent of cancers confined to the head of the pancreas and 70 per cent of cancers at other locations within the gland were detected by ultrasound examination. The correct ultrasound diagnosis was given for fifteen of seventeen patients with resectable pancreas cancer, the degree of associated pancreatitis ranging from minimal to severe. Analysis of the predictive values of positive and negative ultrasound examinations suggests that this test could be used to screen a population of patients with symptoms mildly suggestive of pancreas cancer. The importance of preselecting the level of confidence of a positive test result, a,ove which further investigation is indicated, is emphasized.

Diagnosis, Differential↗
PubMed2006

[Space-occupying lesion of the pancreas--how frequently not due to a suspected ductal adenocarcinoma?].

In patients with a space-occupying lesion of the pancreas at first a primary ductal adenocarcinoma is considered as the cause. Other tumours or metastases are assumed to occur very rarely. Therapy and prognosis of other pancreas tumours differ from therapy and prognosis of a primary ductal adenocarcinoma. We therefore examined the question of how frequently a space-occupying lesion of the pancreas was not due to a ductal adenocarcinoma in our case materials. Retrospectively 70 patients who had undergone a percutaneous puncture of a space-occupying mass of the pancreas under ultrasonographic control were included in the study (34 women, 36 men). In 62 patients a clear histological diagnosis was possible on the basis of the biopsy. In 53 cases (76 %) a primary adenocarcinoma of the pancreas could be diagnosed. In 5 patients (7 %) these masses turned out to be metastases of a previously known malignant tumour disease (2 x mammary carcinoma, 2 x gastric carcinoma, 1 x sigmoid carcinoma). Other tumours could be detected in 4 cases (6 %) including a tuberculoma, an endocrine tumour, a fusocellular sarcoma with partial neurogenic differentiation and a large-cell and pleomorphic-cell anaplastic, partly sarcomatoid carcinoma. In patients with a space-occupying lesion of the pancreas, tumours other than a ductal adenocarcinoma are not rare. In particular, in cases of a previously known malignant tumour disease a space-occupying lesion of the pancreas can also turn out to be a metastasis. Every other individual tumour entity is rare. Other tumour entities at large, however, are found in daily routine. The preoperative biopsy of space-occupying lesions of the pancreas, therefore, still has a clinical importance for the further therapy planning.

Aged↗
PubMed1987

Modulation of a membrane-associated marker in progenitor cells of human pancreas carcinoma.

For the identification of early steps in the multiphasic process of human pancreas carcinogenesis we have developed a panel of monoclonal antibodies to normal and carcinogen-treated human pancreas cells. One of these, an IgG3 with strong affinity for a membrane-associated 46 kd protein (p-46) in progenitor cells of methylnitrosourea (MNU)-treated human pancreas, was purified by h.p.l.c. and used to study the modulation of this marker in human pancreas carcinogenesis. This protein was undetectable in adult human pancreas, appeared on the cell surface of a small subpopulation of human pancreas explants exposed to MNU, persisted in proliferating cells in hyperplastic foci, and was abundant in anaplastic cells in this model. This marker was associated with cytoplasmic and nuclear membrane of all cells in non-tumorigenic and tumorigenic cell lines derived from these explants. It was present in primary carcinomas of human pancreas but absent in normal pancreas adjacent to tumors. This p-46 marker appears to be organ and species specific since it was undetectable in other normal tissues and their neoplastic counterparts.

Adenocarcinoma↗
PubMed2003

Autonomic nerve changes in the mouse pancreas after pancreatic duct ligation.

INTRODUCTION: The mouse pancreas exhibits distinct atrophy of the exocrine tissue following pancreatic duct ligation. AIM: To investigate changes of innervation in the whole pancreas after pancreatic duct ligation. METHODOLOGY: The mouse pancreatic duct was ligated at 6 weeks of age. Pancreatic tissues were removed 7 days and 14 days after the ligation, fixed by perfusion and immersion with Zamboni solution, and embedded in gelatin. The whole organ was serially sectioned at a thickness of 100 microm, histochemically stained for cholinesterase, and observed by light microscopy. The number and volume of intrapancreatic ganglia, number of ganglion cells, and volume of each ganglion cell in the whole pancreas were quantitated. Some sections were analyzed using transmission electron microscopy after histochemically staining for cholinesterase. RESULTS: In the normal pancreas, ganglia were often situated on the outer surface of the islets of Langerhans. Thick nerve bundles ran along the arteries and emanated thin nerve fibers that surrounded the arterioles. In the atrophied pancreas following pancreatic duct ligation, ganglia remained on the islets of Langerhans as in normal mice, while the nerve fibers appeared dense, bending and curling in a more complex manner. The thin nerves also crossed each other in a complex network. Using morphometry in the pancreas following pancreatic duct ligation, the total ganglion cell number was found to decrease from normal levels. The mean ganglion cell volume in the ligated pancreas was significantly smaller than that in normal mice. As observed by transmission electron microscopy, some ganglion cells in the ligated pancreas were negative for cholinesterase activity but were surrounded by positive staining around the surface. CONCLUSIONS: These results suggest that the function of pancreatic ganglion cells changes with organ atrophy after pancreatic duct ligation.

Animals↗
PubMed1999

Porcine endogenous retroviral mRNAs in pancreas and a panel of tissues from specific pathogen-free pigs.

Pigs are potential providers of donor tissues for xenotransplantation (e.g. of pancreatic islets) in Type 1 diabetes. In this context, our group has studied the use of islets from specific pathogen-free (SPF) pigs as a means of reducing the risks of "conventional zoonosis". Although this approach does not prevent the transmission of pig endogenous retrovirus (PERV) to humans, we attempted to determine the presence of C-type PERV mRNAs for gag, pol, and env subtypes as a first descriptive step in the retroviral characterisation of SPF pig tissues (especially pancreas). Using semiquantitative reverse-transcriptase polymer chain reaction with 18S rRNA and beta-actin as internal controls, PERV mRNA levels were compared in a large panel of tissues from SPF and conventional pigs. PERV mRNAs for gag, pol, env-A and env-B were present in all tissues studied from the nine SPF pigs tested. Signals for env-C mRNAs were of much lower intensity than those for env-A and B, and most often undetectable in pancreas. The mRNA levels for gag, pol, env-A, env-B and env-C mRNAs were lower in pancreas (p < 0.01) than in all other tissues. Among other porcine tissues likely to be grafted in man, the highest retroviral mRNA levels were detected in kidney (p < 0.01), followed by liver, lung and heart. Amplified PERV mRNA signals were about 17 times less frequent in pig pancreas than in the retroviral-producing porcine cell line G2, while kidney contained about 6 times more PERV mRNAs than pancreas. The levels of gag, pol, env-A, env-B, and env-C mRNAs also varied between tissues of conventional pigs: PERV mRNA levels were lowest in pancreas, and env-C mRNAs were most often undetectable. For all SPF tissues tested, pol, gag, env-A, env-B, and env-C mRNA levels were in the same range or slightly higher than in corresponding tissues of conventional pigs. In summary, this study of C-type PERV mRNAs in a large panel of tissues from SPF pigs, in the context of our strategy of quality assurance and sanitary control, indicated that PERV mRNA levels were in the same range in SPF and corresponding conventional pig tissues, confirming that the use of SPF pigs would not prevent the risk of PERV transmission to human recipients of xenografts. PERV-A and PERV-B may be mainly represented, and PERV-C much less, in these pig tissues (particularly pancreas). The fact that pancreas expressed the lowest PERV mRNA levels and kidney the highest, among porcine tissues likely to be grafted, could be of interest from a clinical point of view. Pig tissues may differ in their loads of PERV sequences, which could be a factor in the risk of PERV transmission during xenotransplantation.

Animals↗
PubMed1993

Differential regulation of glucokinase and GLUT-2 glucose transporter gene expression in pancreas and liver from neonatal and 16 day old rats.

Glucokinase and GLUT-2 high Km glucose transporter gene expression were studied in pancreas and liver from 2 day old neonatal and 16 day old rats. In pancreas tissue the glucokinase gene was transcribed into a 2.8 kb and a 4.4 kb mRNA species. However, while the 2.8 kb transcript was expressed already in pancreas from 2 day old neonatal rats, distinct expression of the 4.4 kb transcript occurred only in the pancreas from 16 day old rats. GLUT-2 glucose transporter was expressed already in the pancreas from 2 day old neonatal rats, albeit to a lesser extent than in the pancreas from 16 day old rats. Liver glucokinase gene was not expressed in 2 day old neonatal rats but in 16 day old neonatal rats, whereas the GLUT-2 glucose transporter gene was expressed both in the liver from 2 day old neonatal and 16 day old rats. The differences between glucokinase gene expression in neonatal pancreas and neonatal liver provide an indication for a different function of this enzyme in the two tissues. The immature insulin secretory response to glucose in neonatal pancreas may be related to a deficient glucokinase and probably also to a reduced GLUT-2 glucose transporter gene expression.

Aging↗